We have tested the hypothesis that the imperfect correlation between the occurrence of plasma motilin peaks and the migrating motor complex (MMC) is related to the site of origin of the MMC. Gastric and small-intestinal motor activity was recorded manometrically in 16 normal subjects after an overnight fast. Blood samples were taken every 10 min and assayed for motilin. Fifty MMCs were recorded: 29 (58%) originated in the antrum and 21 (42%) in the small intestine. For gastric MMCs a motilin peak (45 +/- 5 pM) was found 10 min before the occurrence of the MMC in the duodenum. For intestinal MMCs no peak could be demonstrated. On an individual basis 27 of the 29 gastric activity fronts were associated with a motilin peak, versus 5 out of 21 intestinal MMCs. It is concluded that in man only gastric activity fronts are associated with plasma motilin peaks. Apparently, motilin is only involved in the regulation of the MMCs originating from the stomach.